Vitamin K1 mediates the postribosomal, structural completion of the critical blood coagulation factors II (prothrombin), VII, IX and X to biologically active forms by mechanisms which have not been fully elucidated. Warfarin, a widely employed human oral anticoagulant and rodenticide, antagonizes vitamin K1 dependent processes by mechanisms which also have not been unambiguously defined. A comprehensive in vitro investigation of the parameters responsible for the differential metabolism of the R and S warfarin enantiomers by the hepatic microsomal mixed function oxidase systems of noninduced and induced rats will be undertaken. The results of these investigations will be correlated with the in vivo pharmacological expression of R and S warfarin in noninduced and induced rats to determine the species of the warfarin enantiomers responsible for antivitamin K1 activity. Once the active species of R and S warfarin has been determined, preliminary experiments will be initiated using warfarin as a probe to determine the pathways utilized by vitamin K1. The R and S warfarin enantiomers will also serve as probes for investigating the multiplicity of cytochrome P-450 species of the hepatic mixed function oxidase system as well as aid in the elucidation of the specific cytochrome P-450 species induced by a variety of chemical and medicinal agents. Collectively the results of these investigations should provide insight into the general mechanisms of warfarin mediated vitamin K1 antagonism as well as those of microsomal drug metabolism.